Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium / 中国结合医学杂志

OBJECTIVE@#To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.@*METHODS@#A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.@*RESULTS@#DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).@*CONCLUSION@#DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Effectiveness and Safety of Chinese Medicinal Injection in Treatment of Unstable Angina Pectoris Based on Network Meta-analysis / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the clinical effectiveness and safety of Chinese medicinal injection （CMI） in the treatment of unstable angina pectoris （UAP）. MethodEight databases， i.e.， China National Knowledge Infrastructure （CNKI），VIP，Wanfang Data，CBM，PubMed，EMBASE，The Cochrane Library，and Web of Science were searched for randomized controlled trials （RCT） of conventional treatment combined with CMI （treatment group） versus conventional treatment （CT）（control group）in the treatment of UAP published from database inception to March 31th 2021. Stata 16.0 was used for network Meta-analysis. ResultThirty-nine RCT involving 3 407 patients were included. As revealed by the results of network Meta-analysis， in terms of the total effective rate in angina pectoris improvement， the therapeutic protocols were ranked as Tanreqing injection（TRQI）+CT>Xiangdan injection（XDI）+CT>Ciwujia injection（CWJI）+CT=Shengmai injection（SMI）+CT>Xuesaitong injection（XSTS）+CT>Breviscapine injection（BI）+CT>Shuxuetong injection（SXTI）+CT>Kudiezi injection（KDZI）+CT>Shuxuening injection（SXNI）+CT>Danshen injection （DSI）+CT>Guanxinning injection（GXNI）+CT>Dengzhanxixin injection（DZXXI）+CT>Xueshuantong injection（XSTI）+CT>Gualoupi injection（GLPI）+CT>CT；for the total effective rate in ECG improvement， SXTI+CT>XDI+CT>TRQI+CT>CWJI+CT>XSTI+CT>BI+CT>XSTI+CT>SXNI+CT>GXNI+CT>KDZI+CT>DZXXI+CT>GLPI+CT>CT>SMI+CT；for the adverse reactions， DZXXI+CT>XDI+CT>DSI+CT>BI+CT>SMI+CT>SXNI+CT>CT>GLPI+CT>GXNI+CT>SXTI+CT>KDZI+CT>CWJI+CT；for the reduction of fibrinogen （FIB）， BI+CT>SXTI+CT>XSTI+CT>CT>KDZI+CT；for the reduction of C-reactive protein （CRP）， DSI+CT>DZXXI+CT>XSTI+CT>CT；for the reduction of high-sensitivity C-reactive protein （hs-CRP）， SXNI+CT>KDZI+CT>SXTI+CT>DZXXI+CT>GLPI+CT>TRQI+CT>XSTI+CT>CT. The results of subgroup analyses were consistent with those of the overall Meta-analysis. ConclusionCMI combined with CT can improve angina pectoris and ECG，reduce adverse reactions，and also improve FIB，CRP，and hs-CRP to varying degrees. However，due to the differences in the quality and quantity of CMIs in RCTs，clinical application should be performed based on the specific conditions.

Effect of Danhong Injection () on Improving Coronary Microcirculation Injury after Percutaneous Coronary Intervention / 中国结合医学杂志

OBJECTIVE@#To explore the effectiveness of Danhong Injection () on improving microcirculatory injury after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD).@*METHODS@#A randomized controlled trial was conducted and 90 patients were enrolled. A random sequence was generated using statistical analysis software. Patients with microcirculatory injuries after PCI were randomly divided into 3 groups for treatment (30 subjects in each group): Danhong Injection group: after PCI, Danghong Injections were given with intravenous administration with 40 mL twice a day for a week; statins intensive group: after PCI, atorvastatin calcium tablets were given oral medication with 80 mg once, and then atorvastatin 40 mg daily for 1 week; the control group: after PCI, atorvastatin calcium tablets were given oral medication with 10-20 mg daily for 1 week. The index of microcirculation resistance (IMR) was used to assess microcirculatory injury during PCI. The IMR of the target vessel was reexamined after 1 week of drug treatment.@*RESULTS@#After one week's drug treatment, IMR was significantly decreased in both statins intensive group and Danhong Injection group compared with the control group (P<0.01), but no difference was found between statins intensive group and Danhong injection group (14.03 ± 2.54 vs. 16.03 ± 5.72 U, P=0.080).@*CONCLUSIONS@#The efficacy of Danhong Injection is non-inferior to statin. Early use of Danhong Injection after PCI can effectively improve coronary microcirculation injury after PCI.

Acute Myocardial Infarction in Chinese Medicine Hospitals in China from 2006 to 2013: An Analysis of 2311 Patients from Hospital Data / 中国结合医学杂志

OBJECTIVE@#To assess the trends in characteristics, treatments, and outcomes of acute myocardial infarction (AMI) patients in tertiary Chinese medicine (CM) hospitals in China between 2006 and 2013.@*METHODS@#This retrospective study was based on two nationwide epidemiological surveys of AMI in tertiary CM hospitals during 2 years (2006 and 2013). Patients admitted to the hospital for AMI were enrolled. Hospital records were used as the data source. Case data were derived regarding baseline characteristics, treatments, and outcomes of patients to assess changes from 2006 to 2013. Logistic regression was used to analyze the relationship between prognosis, general influencing factors of disease, and various treatment measures.@*RESULTS@#Totally 26 tertiary CM hospitals in 2006 and 29 tertiary CM hospitals in 2013 (18 were repetitive) were surveyed. A total of 2,311 patients with AMI were enrolled (1,094 cases in 2006 and 1,217 cases in 2013). From 2006 to 2013, the mean age did not significantly change, but the proportion of patients younger than 65 years increased. The prevalence of risk factors such as hypertension, diabetes, and hyperlipidemia also increased. Significant increases were observed in primary percutaneous coronary intervention [20.48% (2006) vs. 24.90% (2013)] and revascularization [36.11% (2006) vs. 52.42% (2013)]. In-hospital mortality decreased from 11.15% in 2006 to 10.60% in 2013. A mortality logistic regression analysis identified reperfusion therapy [odds ratio (OR), 0.222; 95% confidence interval (CI), 0.106-0.464], Chinese patent medicines (OR, 0.394; 95% CI, 0.213-0.727), and CM decoctions (OR, 0.196; 95% CI, 0.109-0.353) as protective factors.@*CONCLUSION@#Reperfusion and revascularization capabilities of tertiary CM hospitals have improved significantly, but in-hospital mortality has not significantly decreased. Efforts are needed to improve medical awareness of AMI and expand the use of CM to reduce in-hospital mortality in China.

Effects of Danhong Injection () on Peri-Procedural Myocardial Injury and Microcirculatory Resistance in Patients with Unstable Angina Undergoing Elective Percutaneous Coronary Intervention: A Pilot Randomized Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the effect of Danhong Injection (, DH) on the index of microcirculatory resistance (IMR) and myocardial injury in patients with unstable angina undergoing elective percutaneous coronary intervention (PCI).@*METHODS@#Seventy-eight patients with unstable angina were randomly divided into DH group (39 cases) and the control group (39 cases) during elective PCI. Randomization was performed using a random-number table. The DH group received DH at a dosage of 40 mL (mixed with 250 mL saline, covered by a light-proof bag, intravenous drip) during PCI and daily for 7 consecutive days, while the control group only received the same dosage of saline. Both groups received standardized treatment. The IMR and fractional flow reserve (FFR) were measured at maximal hyperemia before and after PCI. Myocardial markers, including myoglobin, creatine kinase (CK), creatine kinase MB (CK-MB), and coronary troponin T (cTnT) values were measured at baseline and 24 h after PCI.@*RESULTS@#Among the 78 patients enrolled, the baseline and procedural characteristics were similar between the two groups. There was no significant difference in pre-PCI myocardial markers and coronary physiological indexes between the two groups. However, post-PCI CK and CK-MB levels in the DH group were significantly lower than those in the control group (111.97 ± 80.97 vs. 165.47 ± 102.99, P=0.013; 13.08 ± 6.90 vs. 19.75 ± 15.49, P=0.016). Post-PCI myoglobin and cTNT-positive tend to be lower in the DH group than in the control group but did not reach statistical significance (88.07 ± 52.36 vs. 108.13 ± 90.94, P=0.52; 2.56% vs.7.69%, P=0.065). Compared with the control group, the post-IMR levels of the DH group tended to decrease, but there was no statistical difference (20.73 ± 13.15 vs. 26.37 ± 12.31, P=0.05). There were no statistical differences in post-FFR in both groups. The peri-procedural myocardial injury of the DH group was significantly lower than that of the control group (2.56% vs. 15.38%, P=0.025). During the 30-d follow-up period, no major adverse cardiovascular events occurred in either group.@*CONCLUSION@#This study demonstrated benefit of DH in reducing myocardial injury and potential preserving microvascular function in patients with unstable angina undergoing elective PCI.